EFFECTS OF FLECAINIDE, ENCAINIDE, AND CLOFILIUM ON VENTRICULAR REFRACTORY PERIOD EXTENSION BY TRANSCARDIAC SHOCKS

Objective: The mechanisms by which pharmacological agents alter electr ical defibrillation are not fully understood. It has been proposed tha t, in addition to directly stimulating tissue, defibrillation may invo lve refractory period extension (RPE) produced by the shock. According ly, pharmacological agents might modulate defibrillation by altering R PE. This study examined the effect of Class I and Class III antiarrhyt hmic agents on RPE by transcardiac shocks. Methods: In four groups of pentobarbital anesthetized dogs, RPE was measured during rapid ventric ular pacing before and after administration of either the Class I agen ts flecainide (n = 7) or encainide (n = 7), the Class III agent clofil ium (n = 7), or vehicle (n = 5). Measurements included QRS duration du ring sinus rhythm and a conduction time, QT(c) interval and refractory period, and RPE for 4- to 10-V/cm shocks delivered 20-80 ms before th e end of the tissue absolute refractory period. For the 6-V/cm shocks, the interval after the shock during which tissue remained refractory (RIAS) was also computed. Results: Drugs affected QRS duration, conduc tion time, QT(c), and refractory period (without shocks) in accordance with their anticipated Class I and Class III actions. Without drugs, significant RPE was observed in all animals for all shocks delivered 4 0 ms or less before the end of the refractory period. Clofilium, encai nide, and flecainide had a tendency to increase RPE but only clofilium produced a significant increase. For 6-V/cm shocks with different tim ings, the minimum RIAS was found to be approximately 43 ms, and occurr ed for shocks given 20-30 ms before the end of the refractory period. Conclusions: At drug dosages that produced moderate Class III (approxi mate to 15%) or strong Class I (approximate to 35%) effects, only the Class III agent significantly increased RPE and RIAS. Thus, in additio n to altering tissue excitability, the effect of antiarrhythmic agents to increase RPE and the minimum RIAS may help explain their influence on defibrillation threshold.